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81.
Fahima?M.?Hashem Mohamed?Nasr Gihan?Fathy Aliaa?IsmailEmail author 《AAPS PharmSciTech》2016,17(3):727-734
The objective of this study was to prepare and evaluate terbutaline sulphate (TBS) bi-layer tablets for once-daily administration. The bi-layer tablets consisted of an immediate-release layer and a sustained-release layer containing 5 and 10 mg TBS, respectively. The sustained-release layer was developed by using Compritol®888 ATO, Precirol® ATO 5, stearic acid, and tristearin, separately, as slowly eroding lipid matrices. A full 4?×?22 factorial design was employed for optimization of the sustained-release layer and to explore the effect of lipid type (X 1), drug–lipid ratio (X 2), and filler type (X 3) on the percentage drug released at 8, 12, and 24 h (Y 1, Y 2, and Y 3) as dependent variables. Sixteen TBS sustained-release matrices (F1–F16) were prepared by melt solid dispersion method. None of the prepared matrices achieved the targeted release profile. However, F2 that showed a relatively promising drug release was subjected to trial and error optimization for the filler composition to develop two optimized matrices (F17 and F18). F18 which consisted of drug–Compritol®888 ATO at ratio (1:6 w/w) and Avicel PH 101/dibasic calcium phosphate mixture of 2:1 (w/w) was selected as sustained-release layer. TBS bi-layer tablets were evaluated for their physical properties, in vitro drug release, effect of storage on drug content, and in vivo performance in rabbits. The bi-layer tablets showed acceptable physical properties and release characteristics. In vivo absorption in rabbits revealed initial high TBS plasma levels followed by sustained levels over 24 h compared to immediate-release tablets. 相似文献
82.
Corina Shtir Mohammed A. Aldahmesh Saad Al-Dahmash Emad Abboud Hisham Alkuraya Marwan A. Abouammoh Sawsan R. Nowailaty Ghazai Al-Thubaiti E. A. Naim B. ALYounes F. S. Binhumaid A. B. ALOtaibi A. S. Altamimi F. H. Alamer Mais Hashem Mohamed Abouelhoda Dorota Monies Fowzan S. Alkuraya 《Human genetics》2016,135(2):193-200
83.
Hanan E. Shamseldin Abdulrahman Aldeeri Zainab Babay Abdulrahman Alsultan Mais Hashem Fowzan S. Alkuraya 《Human genetics》2016,135(10):1209-1211
The role of plasminogen in preventing thrombosis requires activation by tissue plasminogen activator (t-PA) encoded by PLAT. While case–control associations have been pursued for common variants in PLAT, no disease-causing mutations have been reported. We describe a consanguineous family with two children who died shortly after birth due to complications related to severe hydranencephaly and diaphragmatic hernia. A combined exome/autozygome analysis was carried out with informed consent. We identified a homozygous null mutation in PLAT that abrogated t-PA level in patient cells. This is the first reported human knockout mutation of PLAT. The apparent association with hydranencephaly, diaphragmatic hernia and postnatal lethality requires further validation. 相似文献
84.
Motawi TK Hamed MA Hashem RM Shabana MH Ahmed YR 《Zeitschrift für Naturforschung. C, Journal of biosciences》2012,67(1-2):47-57
The protective and therapeutic effects of Argyreia speciosa Sweet (Convolvulaceae) against ethanol-induced gastric ulcer in rats were evaluated. Ethanolic and water extracts of the aerial plant parts (200 mg/kg body weight) were orally administered daily for seven days prior to or after ulceration with one oral dose of 1 mL absolute ethanol on 24-h empty stomachs. Rats were divided into eleven groups. Group 1 served as control. To groups 2 and 3 each extract was administered. Groups 4 to 6 received each extract or ranitidine (100 mg/kg body weight) prior to ulcer induction. Groups 7 to 9 received each extract or ranitidine post ulcer induction. Groups 10 and 11 were gastric ulcerative rats after one hour and one week of ethanol induction. The evaluation was done through measuring ulcer indices: stomach acidity and volume, lesion counts, mucus, and prostaglandin E2 contents. Oxidative stress marker, i. e. malondialdehyde, glutathione, and superoxide dismutase, were estimated. Certain marker enzymes for different cell organelles, i. e. succinate and lactate dehydrogenases, glucose-6-phosphatase, acid phosphatase, and 5'-nucleotidase, were evaluated. The work was extended to determine the collagen content and the histopathological assessment of the stomach. Gastric ulcer exhibited a significant elevation of the ulcer index, antioxidant levels, collagen content, and the marker enzymes. The water extract attenuated these increments and was more potent as a protective agent, while the ethanol extract exhibited stronger therapeutic potency. In conclusion, A. speciosa acted as antiulcer agent. More detailed studies are required to identify the compounds responsible for the pharmacological effect. 相似文献
85.
Lettie E. Rawlins Hashem Almousa Shazia Khan Stephan C. Collins Miroslav P. Milev Joseph Leslie Djenann Saint-Dic Valeed Khan Ana Maria Hincapie Jacob O. Day Lucy McGavin Christine Rowley Gaurav V. Harlalka Valerie E. Vancollie Wasim Ahmad Christopher J. Lelliott Asma Gul Binnaz Yalcin Andrew H. Crosby Michael Sacher Emma L. Baple 《PLoS genetics》2022,18(3)
The highly evolutionarily conserved transport protein particle (TRAPP) complexes (TRAPP II and III) perform fundamental roles in subcellular trafficking pathways. Here we identified biallelic variants in TRAPPC10, a component of the TRAPP II complex, in individuals with a severe microcephalic neurodevelopmental disorder. Molecular studies revealed a weakened interaction between mutant TRAPPC10 and its putative adaptor protein TRAPPC2L. Studies of patient lymphoblastoid cells revealed an absence of TRAPPC10 alongside a concomitant absence of TRAPPC9, another key TRAPP II complex component associated with a clinically overlapping neurodevelopmental disorder. The TRAPPC9/10 reduction phenotype was recapitulated in TRAPPC10-/- knockout cells, which also displayed a membrane trafficking defect. Notably, both the reduction in TRAPPC9 levels and the trafficking defect in these cells could be rescued by wild type but not mutant TRAPPC10 gene constructs. Moreover, studies of Trappc10-/- knockout mice revealed neuroanatomical brain defects and microcephaly, paralleling findings seen in the human condition as well as in a Trappc9-/- mouse model. Together these studies confirm autosomal recessive TRAPPC10 variants as a cause of human disease and define TRAPP-mediated pathomolecular outcomes of importance to TRAPPC9 and TRAPPC10 mediated neurodevelopmental disorders in humans and mice. 相似文献
86.
Cecilia M?nsson Paolo Arosio Rasha Hussein Harm H. Kampinga Reem M. Hashem Wilbert C. Boelens Christopher M. Dobson Tuomas P. J. Knowles Sara Linse Cecilia Emanuelsson 《The Journal of biological chemistry》2014,289(45):31066-31076
The human molecular chaperone protein DNAJB6 was recently found to inhibit the formation of amyloid fibrils from polyglutamine peptides associated with neurodegenerative disorders such as Huntington disease. We show in the present study that DNAJB6 also inhibits amyloid formation by an even more aggregation-prone peptide (the amyloid-beta peptide, Aβ42, implicated in Alzheimer disease) in a highly efficient manner. By monitoring fibril formation using Thioflavin T fluorescence and far-UV CD spectroscopy, we have found that the aggregation of Aβ42 is retarded by DNAJB6 in a concentration-dependent manner, extending to very low sub-stoichiometric molar ratios of chaperone to peptide. Quantitative kinetic analysis and immunochemistry studies suggest that the high inhibitory efficiency is due to the interactions of the chaperone with aggregated forms of Aβ42 rather than the monomeric form of the peptide. This interaction prevents the growth of such species to longer fibrils and inhibits the formation of new amyloid fibrils through both primary and secondary nucleation. A low dissociation rate of DNAJB6 from Aβ42 aggregates leads to its incorporation into growing fibrils and hence to its gradual depletion from solution with time. When DNAJB6 is eventually depleted, fibril proliferation takes place, but the inhibitory activity can be prolonged by introducing DNAJB6 at regular intervals during the aggregation reaction. These results reveal the highly efficacious mode of action of this molecular chaperone against protein aggregation, and demonstrate that the role of molecular chaperones can involve interactions with multiple aggregated species leading to the inhibition of both principal nucleation pathways through which aggregates are able to form. 相似文献
87.
A novel spectrofluorimetric method for determination of imatinib in pure,pharmaceutical preparation,human plasma,and human urine 下载免费PDF全文
The following paper represents a simple, highly sensitive, responsive validated and developed spectrofluorimetric method for estimation of imatinib (IMB) in its pure, commercial preparation, human urine and human blood plasma. The calibration curve was in the range 4–900 ng ml?1 for pure form and urine and 8–900 ng ml?1 for plasma in a medium contains carboxymethyl cellulose (CMC) and acetate buffer (pH 5) with excitation wavelength (λex) 230 nm and emission wavelength (λem) 307 nm. The limit of detection (LOD) was 0.37 ng ml?1 for the pure form, 0.64 ng ml?1 for human urine, and 0.70 ng ml?1 for human plasma, while the limit of quantitation (LOQ) was 1.2 for pure form, 1.91 for urine and 2.1 for plasma. The suggested method was successfully applied for evaluation of IMB in tablets within 99% mean percentage recovery. The excipients that are usually used as additives in pharmaceutical dosage form did not interfere with the suggested method. The method was efficiently used for estimation of IMB in human urine and human plasma. The effect of some cations that might be present in urine and plasma was also studied. The method was also focused on human volunteers and in vitro drug release. 相似文献
88.
89.
Mohammed A. Mansour Wafaa M. Ibrahim Eman S. Shalaan Afrah F. Salama 《Journal of biochemical and molecular toxicology》2019,33(8)
Hexokinase‐2 is overexpressed in several carcinomas including breast cancer to sustain energy for rapidly dividing cells and associates with chemoresistance. However, the impact of chemo drugs (alone or in combination) on hexokinase activity and autophagic cell death is unclear. In this report, we used an in vivo murine adenocarcinoma model to validate the effects of As2O3 and cisplatin on hexokinase activity and autophagic cancer cell death. We found that the two drugs inhibit hexokinase activity and induce autophagic marker, beclin 1 expression. Interestingly, combining As2O3 with cisplatin synergistically enhanced these effects and alleviated oxidative stress often encountered in As2O3 treatment. Altogether, our data provide direct evidence that inhibition of hexokinase activity and induction of autophagic cell death are mediating the antineoplastic effects of As2O3 and cisplatin. Our findings raise the potential of combining As2O3 with cisplatin as an approach to augment cisplatin‐induced cell death and combat cisplatin chemoresistance in cancer. 相似文献
90.
Insulin-like growth factor I stimulates recovery of bone lost after a period of skeletal unloading. 总被引:1,自引:0,他引:1
Benjamin M Boudignon Daniel D Bikle Pam Kurimoto Hashem Elalieh Shigeki Nishida Yongmei Wang Andrew Burghardt Sharmila Majumdar Benjamin E Orwoll Clifford Rosen Bernard P Halloran 《Journal of applied physiology》2007,103(1):125-131
IGF-I stimulates osteoblast proliferation, bone formation, and increases bone volume in normal weight-bearing animals. During skeletal unloading or loss of weight bearing, bone becomes unresponsive to the anabolic effects of insulin-like growth factor I (IGF-I). To determine whether skeletal reloading after a period of unloading increases bone responsiveness to IGF-I, we examined bone structure and formation in response to IGF-I under different loading conditions. Twelve-week-old rats were divided into six groups: loaded (4 wk), unloaded (4 wk), and unloaded/reloaded (2/2 wk), and treated with IGF-I (2.5 mg x kg(-1) x day(-1)) or vehicle during the final 2 wk. Cortical bone formation rate (BFR), cancellous bone volume and architecture in the secondary spongiosa (tibia and vertebrae), and total volume and calcified volume in the primary spongiosa (tibia) were assessed. Periosteal BFR decreased during unloading, remained low during reloading in the vehicle-treated group, but was dramatically increased in IGF-I-treated animals. Cancellous bone volume decreased with unloading and increased with reloading, but the effect was exaggerated in the tibia of IGF-I-treated animals. Total and calcified volumes in the primary spongiosa decreased during unloading in the vehicle-treated animals. IGF-I treatment prevented the loss in volume. These data show that reloading after a period of skeletal unloading increases bone responsiveness to IGF-I, and they suggest that IGF-I may be of therapeutic use in patients who have lost bone as a consequence of prolonged skeletal disuse. 相似文献